{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:50:43Z","timestamp":1792795843511,"version":"4.5.0"},"reference-count":8,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,1,28]],"date-time":"2016-01-28T00:00:00Z","timestamp":1453939200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,1,28]],"date-time":"2016-01-28T00:00:00Z","timestamp":1453939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Repetitive application of topical imiquimod is used as an experimental model for the induction of psoriasiform skin lesions in mice. The model is characterized by several inflammatory processes, including cytokine production both locally and systemically, cellular infiltration and splenomegaly. To investigate the production of type I interferons in response to imiquimod-containing Aldara cream, IFN\u03b2-luciferase reporter mice were imaged <jats:italic>in vivo<\/jats:italic> and <jats:italic>ex vivo<\/jats:italic>. Type I interferons were found to be produced in the skin, but also in the intestinal system caused by unintended ingestion of imiquimod by the mice. Through the use of Elizabethan collars to prevent ingestion, these effects, including psoriasiform lesions were nearly completely prevented. Our findings reveal that topical treatment with Aldara induces a psoriasiform skin inflammation, but that its mode of action depends on ingestion of the chemical, which leads to systemic responses and affects local inflammation. Therefore, potential ingestion of topical treatments during experimental procedures should be taken into account during assessment of cutaneous inflammatory parameters in skin disease models.<\/jats:p>","DOI":"10.1038\/srep20134","type":"journal-article","created":{"date-parts":[[2016,1,28]],"date-time":"2016-01-28T10:40:16Z","timestamp":1453977616000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Topical imiquimod yields systemic effects due to unintended oral uptake"],"prefix":"10.1038","volume":"6","author":[{"given":"Lynda","family":"Grine","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Steeland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Van Ryckeghem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlies","family":"Ballegeer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Lienenklaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siegfried","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niek N.","family":"Sanders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roosmarijn E.","family":"Vandenbroucke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Libert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,1,28]]},"reference":[{"key":"BFsrep20134_CR1","doi-asserted-by":"publisher","first-page":"5836","DOI":"10.4049\/jimmunol.0802999","volume":"182","author":"L van der Fits","year":"2009","unstructured":"van der Fits, L. et al. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23\/IL-17 axis. J. Immunol. 182, 5836\u201345 (2009).","journal-title":"J. Immunol."},{"key":"BFsrep20134_CR2","doi-asserted-by":"crossref","unstructured":"Vinter, H. et al. TNF\u03b1 plays a significant role in the Aldara-induced skin inflammation in mice. Br. J. Dermatol. n\/a\u2013n\/a (2015). 10.1111\/bjd.14320.","DOI":"10.1111\/bjd.14320"},{"key":"BFsrep20134_CR3","doi-asserted-by":"publisher","first-page":"5094","DOI":"10.4049\/jimmunol.1403015","volume":"194","author":"L Grine","year":"2015","unstructured":"Grine, L., Dejager, L., Libert, C. & Vandenbroucke, R. E. Dual Inhibition of TNFR1 and IFNAR1 in Imiquimod-Induced Psoriasiform Skin Inflammation in Mice. J. Immunol. 194, 5094\u20135102 (2015).","journal-title":"J. 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Mechanism of pathogenesis of imiquimod-induced skin inflammation in the mouse: a role for interferon-alpha in dendritic cell activation by imiquimod. J. Dermatol. 41, 135\u201343 (2014).","journal-title":"J. Dermatol."},{"key":"BFsrep20134_CR7","doi-asserted-by":"publisher","first-page":"3229","DOI":"10.4049\/jimmunol.0804277","volume":"183","author":"S Lienenklaus","year":"2009","unstructured":"Lienenklaus, S. et al. Novel reporter mouse reveals constitutive and inflammatory expression of IFN-beta in vivo. J. Immunol. 183, 3229\u201336 (2009).","journal-title":"J. Immunol."},{"key":"BFsrep20134_CR8","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1038\/ncomms2566","volume":"4","author":"A Walter","year":"2013","unstructured":"Walter, A. et al. Aldara activates TLR7-independent immune defence. Nat. Commun. 4, 1560 (2013).","journal-title":"Nat. Commun."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep20134","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep20134.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep20134.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T13:51:14Z","timestamp":1672840274000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep20134"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1,28]]},"references-count":8,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,4,22]]}},"alternative-id":["BFsrep20134"],"URL":"https:\/\/doi.org\/10.1038\/srep20134","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1,28]]},"assertion":[{"value":"16 June 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 December 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"20134"}}